Dichloromethane → Ethyl 6-methoxybenzofuran-3-carboxylate

To a solution of 2-hydroxy-4-methoxybenzaldehyde (45 g, 295.76 mmol) in DCM (80 mL) was added catalytic HBF4 etherate (4 mL, 29.4 mmol) and stirred (rt, 10 min). The reaction mixture was cooled (0° C.) and slowly treated drop wise with ethyl diazoacetate (86 ml, 704.7 mmol) over a 30 minute period while maintaining a controlled temperature (0° C. to 23° C.). The resulting mixture was stirred (rt, 1 h). The reaction mixture was concentrated in vacuo and the resulting dark oil was azeotroped with toluene (200 mL) via rotovap (60° C.). Using a Dean Stark trap, the crude mixture was refluxed (24 h). The reaction was cooled (rt) and concentrated in vacuo. The resulting dark oil was purified by flash column chromatography using EtOAc:hexanes (10%) to provide the title compound as a white solid (24.9 g, 38.2%). MS (ESI): mass calcd. for C12H12O4, 220.2; m/z found, 221.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.16 (s, 1H), 7.90 (d, J=8.6, 1H), 7.03 (d, J=2.2, 1H), 6.98 (dd, J=6.4, 2.3, 1H), 4.39 (q, J=7.2, 2H), 3.86 (s, 3H), 1.41 (t, J=7.2, 3H).

1. temperaturewhile maintaining a controlled temperature (0° C. to 23° C.)
2. stirringThe resulting mixture was stirred (rt, 1 h)
3. concentrationThe reaction mixture was concentrated in vacuo
4. customthe resulting dark oil was azeotroped with toluene (200 mL) via rotovap (60° C.)
5. temperaturethe crude mixture was refluxed (24 h)
6. temperatureThe reaction was cooled (rt)
7. concentrationconcentrated in vacuo
8. customThe resulting dark oil was purified by flash column chromatography

ORD record

ord-8a6688e40d69420fac71567a4d7f28c8

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399465B2